17  mb  1915 


The  Valence  of  Nitrogen  in  Am- 
monium Salts 


BY 

RALPH  S.  POTTER 

A.B.  Lake  Forest  College,  1909 
M.S.  University  of  Illinois,  1911 


A THESIS 

SUBMITTED  IN  PARTIAL  FULFILMENT  OF  THE  REQUIREMENTS  FOR 
THE  DEGREE  OF  DOCTOR  OF  PHILOSOPHY  IN  CHEMISTRY 
IN  THE  GRADUATE  SCHOOL  OF  THE  UNI- 
VERSITY OF  ILLINOIS 
1913 


Easton,  Pa.  : 

Eschenbach  Printing  Company 
1914 


Digitized  by  the  Internet  Archive 
in  2017  with  funding  from 

University  of  Illinois  Urbana-Champaign  Alternates 


https://archive.org/details/valenceofnitroge00pott_0 


u ns  z‘Ti 


The  Valence  of  Nitrogen  in  Ammonium 

Salts 


During  the  early  years  of  the'  development  of  the  theory  of  valence, 
many  chemists  held  the  view  that  each  element  has  an  unvarying  valence. 
The  apparent  change  of  valence  in  nitrogen  from  ammonia  to  ammonium 
salts,  and  in  phosphorus  from  phosphorus  trichloride  to  phosphorus  penta- 
ehloride  was  explained  by  calling  the  ammonium  salts  and  the  pentaehloride 
molecular  compounds,  as  distinguished  from  ammonia  and  the  trichloride, 
in  which  the  true  valence  of  the  elements  was  supposed  to  be  shown. 
This  view  received  support  from  the  dissociation  of  ammonium  salts 
and  of  phosphorus  pentaehloride  in  the  gaseous  state.  Gradually,  with 
the  demonstration  that  phosphorus  pentaehloride  volatilizes  in  part  un- 
changed, that  phosphorus  pentafluoride,  PF5,  has  a vapor  density  corre- 
sponding to  its  formula  and,  in  general,  that  dissociation  in  the  gaseous 


4 


state  does  not  correspond  to  any  rational  distinction  between  unitary  and 
molecular  compounds,  the  view  that  elements  may  show  a varying  valence 
in  their  compounds  and  that  nitrogen  and  phosphorus  are  sometimes  triva- 
lent  and  sometimes  quinquivalent,  came  to  be  generally  accepted. 

More  recently,  Werner1  has  proposed  a modified  molecular  formula 
for  ammonium  chloride,  H3N  • • HC1.  By  this  formula  he  intends  to  indi- 
cate that  in  the  ammonium  salts  the  nitrogen  atom  retains  a normal  valence 
of  three,  but  that  the  nitrogen  atom  of  the  ammonia  and  the  hydrogen  atom 
of  the  hydrochloric  acid  are  held  together  by  secondary  (“Neben”) 
valences,  the  hydrogen  and  chlorine  of  the  acid  retaining  essentially  the 
same  relation  to  each  other  as  in  the  free  acid. 


An  amino  acid  may,  theoretically,  assume  in  the  aqueous  solution  the 


'C02H 


following  forms:  a,  the  free  acid,  R\  ; b}  a cyclic  salt,  JRn. 

xnh2  xnh3/ 


O, 


/ 


CO  — o 


or  according  to  Werner,  R\ 

\ 


: ; c,  a bimolecular  or  polymolecular 
NH2 — H 

/C02— H3Nv 

salt  formed  by  the  union  of  two  or  more  molecules,  R\  /R; 

xnh3— o2cr 

vC02“ 

d,  the  ions  of  the  acid  group  R\  and  H+;  e , the  ions  of  the  base, 

XNH2 

/C02H  /C02- 

R\  and  OH~ ; /,  the  double,  amphoteric  ion,  R\  .2 

xnh3+  xnh3+ 

The  “inner  salt”  structure  was  first  proposed  by  Erlenmeyer  and 
Siegel3  in  1875.  Ten  years  later  Ostwald4  noticed  that  solutions  of  glyco- 
coll,  CH2NH2C02H,  have  a very  low  molecular  conductivity  and  that  this 
is  only  slightly  increased  by  dilution.  He  states  that  in  its  behavior  it 
is  more  like  a neutral  salt  than  an  acid.  In  1891  Marckwald5  called  at- 
tention to  the  fact  that  amino  acids  of  the  aliphatic  series  react  only  slowly 
with  the  mustard  oils,  while  other  primary  amines  react  quite  readily. 
Since  the  amino  acids  react  easily  in  alkaline  solutions,  he  held  that  the 
acids  are,  in  reality,  inner  salts.  Sakurai6  attempted  to  substantiate  the 
“inner  salt”  structure  on  their  preparation  from  halogen  derivatives  of 
the  acids  and  on  the  resistance  which  amino  acids  offer  to  the  formation 
of  acid  chlorides.  Walker7  points  out  that  conductivity  determinations 


1 See  Neuere  Anschauungen  auf  dem  Gebiet  der  anorganischen  Chemie,  1905,  p.  96. 

2 “Zwitterion.” 

* Ann.,  176,  349  (1875). 

4 J.  prakt.  Chem.,  32,  369  (1885). 

5 Ber.,  24,  3278  (1891). 

6 Proc.  Chem.  Soc.,  10,  90  (1894). 

7 Ibid.,  10,  No.  139  (1895). 


5 


tell  us  very  little  about  the  structure  of  glycocoll,  but  that,  since  the  con- 
ductivity of  phenylgly cocoll,  C6H5NHCH2C02H,  is  greater  than  that 
of  acetic  acid,  it  must  contain  a carboxyl  group  which  ionizes.  Tilden  and 
Forster1  showed  that  the  amino  group  of  amino  acids  may  be  replaced 
by  chlorine  by  the  action  of  nitrosyl  chloride,  and  considered  this  an  argu- 
ment against  the  inner  salt  formation.  Somewhat  later  Carrara  and 
Rossi2  based  an  argument  for  the  inner  salt  structure  on  the  conductivity 
of  betaine  hydrochloride,  (CH3)3NC1CH2C02H.  From  the  values  found 
they  considered  that  the  salt  was  almost  completely  hydrolyzed  to  hydro- 
chloric acid  and  betaine,  (CH3)3NCH2CO.  Winkelblech3  points  out, 

\/ 


however,  that  if  betaine  hydrochloride  is  in  reality  hydrolyzed  the  con- 
ductivity of  the  solution  should  be  the  same  as  that  of  the  equivalent  amount 
of  hydrochloric  acid,  while  both  Bredt’s  measurements  and  those  of  Car- 
rara and  Rossi  gave  a conductivity  scarcely  more  than  one-half  as  great. 
There  can  be  no  doubt,  of  course,  that  the  anhydride  of  betaine, 
(CH3)3NCH2C02,  has  the  structure  of  a salt,  but  no  one  seems  to  have 
determined  whether  this  is  monomolecular  or  dimolecular.  Walker4 


^C02H 


has  shown,  however,  that  aminoacetic  acid,  CH2 


, is  monomolecular 


in  aqueous  solutions.  Our  results,  given  below,  indicate  that  a solution 
of  an  amino  acid  which  gives  no  inner  salt  may  still  contain  the  acid  mostly 
in  the  monomolecular  form. 

Winkelblech5  discusses  the  hydrolysis  of  an  amino  acid  on  the  basis 
of  conductivity  data  for  weak  acids,  weak  bases  and  water.  It  does  not 
seem  possible  from  conductivity  data,  however,  to  determine  whether  the 

/c°2 1 

acid  is  in  the  form  of  an  inner  salt,  R\  , in  the  unionized  state, 

xNH3J 

,co2h  xo2h 

R\  or  R\  , in  the  form  of  the  double,  amphoteric  ion 

XNH2  xnh3oh 

/C02~  /C02 — NHsv 

R\  , or  in  the  form  of  a bimolecular  salt,  R\  /R.  The 

xnh3+  xnh3— co/ 

hydrogen  and  hydroxyl  ions  of  the  amphoteric  form  would,  of  course, 
combine  to  form  water  and  if  the  acid  and  basic  functions  were  of  equal 
“strength”  the  solution  would  react  neutral.  None  of  these  forms  would 
show  any  conductivity  and,  while  the  bimolecular  form  could  be  distin- 


1 Chem.  News,  71,  239  (1895). 

2 Atti  R.  Accad.  Lincei,  [5]  6,  208  (1897). 
* Z.  physik.  Chem.,  36,  590  (1901). 

4 Proc.  Chem.  Soc.,  10,  94  (1894). 

5 Loc.  cit. 


6 


guished  from  the  others  by  a determination  of  the  molecular  weight,  it  is 
not  clear  how  any  of  the  ordinary  physical  methods  could  be  used  to  dis- 


tinguish between  the  three  forms,  R 
XOoH 


/ 


C02H 


'NHo 


/CO2 1 

’ R\  ’ 


/C02- 
and  R\ 

XNH3+ 


The  form  R\  would  have  a higher  molecular  weight  and  might, 

xNH3OH 


possibly,  be  distinguished  from  the  other  three  by  that  means,  but  it  could 
not  be  distinguished  by  conductivity  measurements.  It  does  not  seem 
to  us  that  the  ordinary  equations  for  hydrolysis,  which  Winkelblech  at- 
tempts to  apply,  could  be  used  in  a complex  case  of  this  sort. 

From  the  above  summary  it  would  seem  that  the  evidence  with  regard 
to  inner  salt  formation  is  not  altogether  satisfactory  and  light  upon  the 
question  from  an  entirely  different  point  of  view  is  welcome.  We  think 
that  we  have  secured  this  from  a study  of  the  specific  rotations  of  a series 
of  amino  acids  from  camphor.  The  formulas  and  names  of  the  compounds 
are  given  below.  To  bring  out  the  relationships  more  clearly  the  specific 
rotations  given  for  the  salt  are  calculated  to  the  basis  of  one  gram  of  the 
free  acid  in  1 cc.  of  the  solution  instead  of  for  one  gram  of  the  salt. 


CH2 — C (CH3) — CO  CH2 — C (CH3) — CO 


\ 

\ 

1 

C(CH3)2 

0 

C(CH3)2 

1 

/ 

1 

CH2— CH NHS  CH2— CH NH 

Aminocamphonanic  Acid.  Anhydride  of  Aminocamphonanic 

Md  = — 29. 20.  Acid.  [«]d  = — 60.5°. 


CH2— C(CH3)— co2h 

I I 

I C(CH3)2 

I I 

CH2— CH— NHjCl 
Hydrochloride  of  Aminocamphonanic 
Acid.  [q:]d  = 25. o°. 

CH2— C(CH3)NH3 

I \ 

C(CH3)2  o 

I / 

CH2— CHCO x 

Aminodihydrocampholytic  Acid. 
[«]d  = 53-7  °- 
CH2— C(CH3)NH3C1 

I 

C(CH3)2 

I 

ch2— chco2h 

Hydrochloride  of  Aminodihydro- 
campholytic Acid.  [<x]d  = 41.3°. 


CH2— C(CH3)— C02Na 

I l 

C(CH3)2 

I I 

ch2— chnh2 

Sodium  Salt  of  Aminocamphonanic 
Acid.  [o:]d  = 52.8  °. 

CH2 — C(CH3)— NH 

I 

C(CH3)2 

I 

CH2— CH CO 

Anhydride  of  Aminodihydrocampholytic 
Acid.  [q:]d  = 72.8°. 

CH2— C(CH3)NH2 

I 

C(CH3)2 

I 

CH2— CHC02Na 
Sodium  Salt  of  Aminodihydro- 
campholytic Acid.  [a]D  = 18.3  °. 


7 


% 


CH2— C(CHs)— co2h 

I 

C(OH3)2 

I 

CH2— CH— CH2NH2 
a-Aminocampholic  Acid. 

Md  = 67°. 

CH2— C(CH3)— co2h 

I 

C(CH3)2 

I 

CH. — CH — CH2 — NH3CI 
Hydrochloride  of  a-Aminocampholic 
Acid.  Md  = 44-7°. 

CH2— C (CH3)— ch2nh2 


CH2— CH— C02H 
/3-Aminocampholic  Acid. 

Md  = 16.4  °. 

CH2— C(CH3)— CH2NH3C1 
C(CH3)2 

I 

CHi— CH— C02H 

Hydrochloride  of  /3-Aminocampholic 
Acid.  Md  = 41.3°* 


CH2— C(CH3)CO 

II  V 

C(CHi),  NH 

I / 

CH2— CH CH2 

Anhydride  of  a-Aminocampholic 
Acid  (a-Camphidone).  Md  = — 33-9°. 

CH2— C(CH3)— C02Na 

I 

C(CH3)2 

I 

CHj— CN— CH2— NH, 
Sodium  Salt  of  a-Aminocampholic 
Acid.  Md  = 62.4°. 

CH2— C(CH3)— ch2 

! 1 \ 

C(CH3)2  NH 

I I / 

CH2— CH CO 

Anhydride  of  /3-Aminocampholic  Acid 
(/3-Camphidone).  [a]p  = 66.5°. 

CH2— C (CH3)  ch2nh2 

I I 

C(CH3)2 

I I 

CH2— CH— C02Na 
Sodium  Salt  of  j3-Aminocampholic 
Acid.  Md  = 14.3  °. 


It  will  be  noticed  that  the  aminocamphonanic  acid  and  aminodihydro- 
campholytic  acid  are  represented  as  having  a cyclic  or  inner  salt  structure, 
while  the  aminocampholic  acids  are' both  represented  as  having  an  open 
structure.  The  evidence  for  these  structures  is  based  on  the  specific 
rotation  of  the  compounds.  The  rotation  of  the  sodium  salt  and  hydro- 
chloride of  aminocamphonanic  acid  are  to  the  right  while  that  of  the  an- 
hydride, which  is  undoubtedly  cyclic  in  structure,  is  to  the  left.  The 
ammonium  salt  is  also  left  handed,  indicating  a cyclic  structure  similar 
to  that  of  the  anhydride.  The  sodium  salt  and  hydrochloride  of  amino- 
dihydrocampholytic  acid  are  right  handed.  The  free  acid  and  anhydride 
are  also  right  handed,  but  with  a considerably  increased  rotation.  The 
sodium  salt  and  free  a-aminocampholic  acid  are  both  right  handed  with 
rotations  closely  alike,  indicating  that  each  has  an  open  structure,  but  the 
anhydride,  which  certainly  has  a cyclic  structure,  is  left  handed  and  has 
a rotation  very  closely  like  that  of  the  aminocamphonanic  acid,  indicating 
again  very  clearly  that  the  latter  has  a cyclic  structure  and  that  each 
compound  contains  a cycle  of  six  atoms.  The  sodium  salt  of  /3-aminoeam- 
pholic  acid  and  the  free  acid  also  correspond  closely  in  rotation,  indicating 


8 


an  open  structure  for  both,  while  the  hydrochloride  and  anhydride  have 
a considerably  greater  rotation,  as  is  the  case  with  both  the  free  amino- 
dihydrocampholytic  acid  and  its  anhydride. 

All  of  these  observations  are  consistent  with  the  hypothesis  that  amino- 
dihydrocampholytic  and  aminocamphonanic  acid  form  cyclic  salts  con- 
taining cycles  of  six  atoms,  while  the  aminocampholic  acids  do  not  form 
such  salts,  because,  if  formed,  they  would  contain  cycles  of  seven  atoms. 
It  seems  dfficult  to  find  any  other  simple  explanation  for  the  observations. 

The  results  also  point  very  strongly  to  the  formula  for  ammonium  salts 
which  represents  them  as  containing  quinquivalent  nitrogen  and  against 
Werner’s  formula.  According  to  Werner’s  formula  the  free  aminocam- 
phonanic and  aminodihydrccampholytic  acids  would  contain  cycles  of 
seven  atoms, 

CH2— C (CHs)— CO— O 
C(CH3)2  H 

I i 

CHj— CH NH, 

Such  a formula  is  quite  inconsistent  with  all  that  we  know  about  the  ease 
with  which  rings  of  five  and  six  atoms  are  formed  and  the  comparative 
rarity  of  seven-atom  rings.  It  is  also  inconsistent  with  the  close  agree- 
ment between  the  rotation  of  the  aminocamphonanic  acid  and  that  of  the 
anhydride  of  a-aminocampholic  acid.  We  know  that  the  latter  compound 
contains  a six-atom  ring. 

Determinations  of  the  molecular  weights  in  aqueous  solutions  by  the 
freezing  point  method  have  shown  that  all  four  of  the  amino  acids  are 
monomolecular  in  such  solutions. 

The  following  table  brings  out  in  a striking  way  the  relations  which  have 
been  found.  The  rotations  are  calculated  from  results  obtained  with 
solutions  containing  from  2.5  to  10%  of  the  substances  examined  and  are 
given  on  the  basis  of  the  amount  of  free  amino  acid  corresponding  to  the 
compound  which  was  present.  Thus  [a]D  for  the  hydrochloride  of 
aminocamphonanic  acid  (i.  e.,  the  rotation  in  a 10  cm.  tube  of  1 g.  in  1 cc.) 
is  25.0 0 but  the  rotation  in  the  table  is  given  as  30.3 °,  which  is  the  calcu- 
lated rotation  for  1 g.  of  the  free  acid  in  1 cc.,  after  conversion  into  the 
hydrochloride. 

HCl  HC1 


HCl 

Free 

salt  + 

1 mol 

salt  + 

2 mols 

Anhy- 

salt. 

acid. 

NaOH. 

NaOH. 

dride. 

Aminocamphonanic  acid 

..  30. 3° 

— 29. 2° 

—28.8° 

55-4° 

—60.5° 

Aminodihydrocampholytic  acid . . . . 

..  50.1° 

54-7° 

54-0° 

20. 50 

72.8° 

a- Aminocampholic  acid 

••  53-3° 

67.0° 

62.4° 

65-6° 

—33-9° 

/3- Aminocampholic  acid 

••  49-5° 

16. 40 

16. 7° 

15-2° 

66.5° 

The  free  acids  have,  in  each  case,  nearly  the  same  rotation  when  prepared 
by  the  addition  of  one  mol  of  sodium  hydroxide  to  one  mol  of  the  hydro- 


9 


chloride,  as  when  the  pure  acid  is  dissolved  directly  in  water.  The  addi- 
tion of  a second  mol  of  sodium  hydroxide  causes  a large  change  in  the  ro- 
tations of  aminocamphonanic  and  aminodihydrocampholytic  acids,  evi- 
dently because  the  cyclic  structure  of  the  inner  salt  is  broken  down  by  the 
formation  of  the  sodium  salt,  but  no  such  change  is  observed  with  the 
campholic  acids. 

Experimental. 

/C02H 

Aminocamphonanic  Acid,  CgHiX  . — The  hydrochloride  of  amino- 

XNH2 

camphonanic  acid  was  prepared  as  previously  described.1  One  hundred 
grams  of  the  hydrochloride  were  dissolved  in  water  and  a solution  of  so- 
dium hydroxide  added  till  the  reaction  was  faintly  alkaline  to  phenolphthalein 
after  boiling  a small  portion  in  a test  tube.  The  solution  was  then  evap- 
orated to  about  ioo  cc.  and  the  free  amino  acid  obtained  was  filtered  off 
and  was  recrystallized  by  dissolving  in  water  and  evaporating  the  solu- 
tion. The  yield  of  the  crude  acid  was  72  g.,  about  82%  of  the  theory. 
It  is  possible  to  recover  the  remainder  of  the  acid  as  hydrochloride  from 
the  mother  liquors.  The  free  acid  is  about  equally  soluble  in  hot  and 
cold  water.  Hoogewerf  and  Van  Dorp2  report  a melting  point  of  260°. 
If  heated  rather  rapidly  we  find  that  it  sublimes  without  melting  at  a 
temperature  above  300  °.  It  is  probable  that  the  melting  point  reported 
by  Hoogewerf  and  Van  Dorp  was  found  by  heating  slowly,  which  causes 
a partial  conversion  into  the  anhydride.  The  latter  melts  at  203  °.  Be- 
cause of  the  melting  point  reported  by  the  authors  mentioned,  and  because 
of  the  left-handed  rotation,  which  seemed  to  us,  at  first,  anomalous  for 
a derivative  of  dextrocamphoric  acid,  the  mother  liquors  from  the  prepara- 
tion of  the  aminocamphonanic  acid  were  very  carefully  examined  for  a 
possible  isomer,  but  none  was  found. 

The  aqueous  solution  of  aminocamphonanic  acid,  10  g.  in  100  cc.  of  the  solution, 
gave  a specific  rotation  [a]^  = — 29. 2 °. 

The  molecular  weight  was  determined  with  a sample  which  had  been 
recrystallized  six  times  from  water,  twice  more  than  was  necessary  to  re- 
move all  of  the  chlorine.  A solution  of  the  acid  was  mixed  with  ice,  from 
distilled  water,  which  had  been  broken  to  pieces  the  size  of  a pea  and  the 
mixture  was  placed  in  a Dewar  bulb.  After  equilibrium  was  reached  and 
the  temperature  had  been  taken,  20  cc.  of  the  clear  solution  were  drawn 
off  and  evaporated  and  the  residue  dried  to  constant  weight  on  the  water 
bath.  The  results  were : 

Subst.,  0.304;  H20,  16.6;  depression,  0.194;  mol.  wt.  found,  173.  Calc,  for 
C8H14C02NH2,  17 1. 

1 Am.  Chem.  J.,  16,  507  (1894).  Formerly  called  aminolauronic  acid.  See  /. 
Am.  Chem.  Soc.,  34,  1067  (1912). 

2 Ibid.,  16,  506  (1874),  footnote. 


IO 


/CO 

The  Anhydride  of  Aminocamphonanic  Acid,  C8Hi4\  I , has  been 

XNH 

prepared1  by  distilling  a mixture  of  the  hydrochloride  and  lime.  The 
following  method  gives  a nearly  quantitative  yield  and  avoids  the  use  of 
a high  temperature:  Ten  grams  of  the  hydrochloride,  6 g.  (1.5  mol)  of 
fused  sodium  acetate,  and  20  cc.  of  acetic  anhydride  were  boiled  gently  in 
a long  necked  flask  for  about  10  min.  After  cooling,  10%  excess  of  a 
strong  solution  of  sodium  hydroxide  was  added  and  the  mixture  heated  on 
the  water-bath  till  the  liquid  layer  which  formed  at  first  on  top  was  changed 
to  a solid.  The  liquid  layer  probably  consisted  in  part  of  the  acetyl  de- 
rivative of  the  anhydride,  but  this  was  not  examined  further.  After  cool- 
ing, the  anhydride  was  separated  by  two  extractions  with  ether.  After 
two  crystallizations  from  petroleum  ether  it  melted  quite  sharply  at 

O 9 

203  .2 

[«]2d°  = — 60.5,  i g.  in  10  cc.  of  absolute  alcohol  and  [a]2D°  = — 60.6  °,  0.05  g. 
in  10  cc.  of  water.  Noyes  and  Taveau3  found  [a]2D°  = — 60.1 0 for  a 10%  alcohol 
solution. 

Subst.,  0.373,  0.750;  H20,  20.9,  20.1;  depression,  0.208°,  0.432  °;  mol.  wt.  found, 
/NH 

157,  159-  Calc,  for  CsH^v  | : 153. 

XCO 

Hydrolysis  of  Aminocamphonanic  Acid  Anhydride.— The  anhydride 
was  not  hydrolyzed  by  heating  with  water  for  three  days  in  a water-bath. 
Heating  for  three  days  in  the  water-bath  with  an  excess  of  sodium  hy- 
droxide was  also  without  effect,  but  when  3 g.  of  the  anhydride  were  heated 
for  10  hrs.  with  20%  hydrochloric  acid  the  solution  deposited  crystals  of 

^ C02H 

the  hydrochloride  of  aminocamphonanic  acid,  C8Hi4\.  , on  cooling. 

XNH3C1 

This  gave  [a] d°  = 24.9°,  proving  that  there  is  no  inversion  of  the  acid 
either  in  the  formation  of  the  anhydride  or  in  its  hydrolysis. 

/CO 

Acetyl  Derivative  of  Aminocamphonanic  Anhydride,  C8Hi4\  I 

xNC2H30 

— This  was  prepared  by  boiling  a mixture  of  6 g.  of  aminocamphonanic 
acid  hydrochloride,  3.5  g.  of  sodium  acetate  and  12  cc.  of  acetic  anhydride 
for  10  min.  After  cooling  and  adding  enough  sodium  hydroxide  to  nearly 
neutralize  the  acetic  acid  and  excess  of  acetic  anhydride,  the  mixture  was 
extracted  with  petroleum  ether  and  the  extract  washed  with  water  to  re- 
move free  acid.  After  drying  with  sodium  sulfate  and  distilling  away  the 

1 J.  Am.  Chem.  Soc.,  34,  62  (1912). 

2 Am.  Chem.  /.,  16,  507  (1894). 

3 Ibid.,  32,  288  (1904). 


petroleum  ether,  a slightly  yellow  oil  was  obtained.  This  was  distilled 
and  the  portion  boiling  at  260-262°  was  analyzed: 

Calc,  for  C8Hi4C0NC2H30:  N = 7.16;  found:  7.05;  [«]d  = +72. 70,  0.544  S-  in 
5 cc.  of  alcohol. 

The  substance  gave  aminocamphonanic  anhydride  melting  at  201-203 0 
by  hydrolysis  with  sodium  hydroxides. 

/CO 

Nitroso  Derivative  of  Aminocamphonanic  Anhydride,  C8Hi4\  I 

xNNO 

— This  was  prepared  by  Bredt,1  but  he  did  not  determine  the  specific 
rotation. 

We  found  [afD4°  = 153  °;  0.25  g.  in  10  cc.  of  alcohol. 

It  is  interesting  to  notice  that  both  the  acetyl  and  the  nitroso  group 
change  the  negative  rotation  of  the  anhydride  to  a positive,  the  nitroso 
group  producing  a much  larger  effect  than  the  acetyl  group. 

/C02H 

Cyanocamphonanic  Acid,  C8Hi4\  , was  prepared  by  treating 

XCN 

/C02H 

o:-camphoramidic  acid,  C8Hi4\  , with  acetyl  chloride,  according 

XCONH2 

to  the  method  of  Hoogewerf  and  Van  Dorp.2  This  gave  about  the  same 
yield  of  crude  acid  which  they  obtained,  namely,  about  50%.  It  was 
thought,  since  the  hydrochloride  of  the  a-isoimide  obtained  by  treating 
the  a-camphoramidic  acid  with  acetyl  chloride  is  very  easily  hydro- 
lyzed by  water  to  the  a-camphoramidic  acid,  that  perhaps  by  suspending 
the  isoimide  hydrochloride  in  petroleum  ether  and  passing  in  dry  ammonia 
gas,  the  yield  could  be  increased.  The  following  procedure  was  used: 
12.5  g.  of  a-camphoramidic  acid  and  50  g.  of  acetyl  chloride  were  placed 
in  a flask  which  was  attached  to  a reflux  condenser.  The  flask  was  heated 
on  the  water  bath.  A solution  is  first  formed  and  in  about  two  minutes 
the  contents  of  flask  apparently  become  solid.  The  flask  and  material 
were  then  cooled,  the  material  filtered  and  the  solid  washed  with  carbon 
disulfide.  Up  to  this  point  the  method  of  procedure  was  just  the  same 
as  given  by  the  above  mentioned  investigators.  Instead  of  adding  the 
isoimide  hydrochloride  to  20%  ammonia,  as  they  did,  it  was  shaken  with 
petroleum  ether  and  a slow  stream  of  dry  ammonia  gas  was  passed  through 
the  mixture  until  saturation  was  reached.  A dilute  solution  of  ammonia 
was  added  to  dissolve  the  ammonium  salts,  and  from  the  aqueous  solution 
the  cyanoacid  was  precipitated  with  dilute  hydrochloric  acid.  The 
hydrochloric  acid  solution  must  be  added  drop  by  drop  or  the  cyanoacid 
will  be  precipitated  as  a gummy  mass.  The  crystalline  acid  was  filtered 

1 Ber.,  35,  1291  (1902). 

2 Rec.  trav.  chim.,  14,  261  (1895). 


12 


and,  after  drying,  was  weighed,  io  g.,  or  84%,  of  the  theory  was  ob- 
tained. For  purification  two  methods  were  used,  one  by  recrystalliza- 
tion from  hot  water,  which  was  the  method  used  by  Hoogewerf  and 
Van  Dorp,  the  other,  by  dissolving  the  acid  in  dilute  ammonium  hydroxide 
and  precipitating  it  with  dilute  hydrochloric  acid.  By  the  first  method 
from  5 g.  of  the  crude  acid  2.4  g.  of  acid,  melting  sharply  at  12 1°,  were 
obtained.  This  is  the  melting  point  found  by  the  above  mentioned  in- 
vestigators. By  the  second  method,  3.1  g.  of  the  pure  product  were  ob- 
tained from  5 g.  of  the  crude  acid.  This  method  is  also  to  be  preferred 
on  account  of  its  greater  ease  of  manipulation. 

[«]2d°  = 67.3°,  1 g.  in  10  cc.  of  alcohol.  Hoogewerf  and  Van  Dorp1  found  exactly 
the  same  for  a 6%  alcoholic  solution. 

X02H 

a-Aminocampholic  Acid  Hydrochloride,  C8Hi4\  . — The  only 

xCH2NH3C1 

variation  from  the  method  of  preparation  of  Hoogewerf  and  Van  Dorp2 
or  Rupe  and  Splittgerber3  was  that  a somewhat  larger  portion  of  sodium 
was  used  in  the  reduction.  5 g.  of  cyanocamphonanic  acid  were  dis- 
solved in  50  cc.  of  absolute  alcohol  and  15  g.  of  sodium  were  added  in  small 
portions,  the  flask  being  connected  to  a reflux  condenser.  During  the 
addition  of  the  sodium  about  20  cc.  more  of  alcohol  were  added.  After 
all  the  sodium  had  dissolved  water  was  added  and  the  solution  was  evap- 
orated until  the  odor  of  alcohol  was  no  longer  given.  From  this  point 
on  a method  of  separation  and  purification  of  the  hydrochloride  entirely 
different  from  that  of  Rupe  and  Splittgerber3  was  used.  Hydrochloric 
acid  in  slight  excess  was  added  to  the  cold  solution  and  it  was  then  ex- 
tracted with  ether  in  order  to  remove  any  unchanged  cyanoacid.  Upon 
evaporation  of  the  ether  solution  it  was  found  that  about  1 g.  of  cyano- 
acid was  obtained.  This  was  used  in  subsequent  reductions.  The 
hydrochloric  acid  solution  was  evaporated  to  dryness  and  the  residue 
ground  up  in  a mortar  with  alcohol.  The  alcohol  was  filtered,  diluted, 
with  water  and  the  alcohol  was  evaporated.  The  brown  turbidity  of  the 
solution  was  then  removed  by  filtering  twice  through  powdered  animal 
charcoal.  The  clear  solution  was  then  evaporated  on  the  water  bath 
until  crystals  started  to  form,  when  it  was  removed  and  allowed  to  cool 
and  filtered.  The  very  slightly  brown  crystals  were  dissolved  in  the 
minimum  amount  of  hot  water,  filtered  again  through  animal  charcoal 
and  after  cooling,  the  pure  white,  needle-like  crystals  were  filtered  off, 
dried,  and  a melting  point  taken.  It  was  found  to  be  248-250°.  A 
portion  was  again  recrystallized  and  the  same  melting  point  was  given. 

1 Rec.  trav.  chim.,  14,  26  (1895). 

2 Ibid.,  14,  261  (1895). 

3 Ber.,  40,  4313  (1907). 


13 


* 


Rupe  and  Splittgerber1  give  the  melting  point  as  247-248  °.  The  specific 
rotation,  which  had  never  been  taken  before,  was  determined. 

[a]2o°  = 44-7°;  0.5  g.  in  10  cc.  of  a solution  in  water. 

Calc,  for  C8H14(C02H)CH2NH2HC1:  Cl  = 16.00;  found:  Cl,  16.17. 

/C02H 

a-Aminocampholic  Acid,  C8Hi4\  . — An  attempt  was  made 

XCH2NH2 


to  prepare  the  free  acid  from  its  hydrochloride  in  the  same  manner  that 
aminocamphonanic  acid  is  prepared  from  its  hydrochloride,  but  the  free 
acid  was  apparently  more  soluble  than  sodium  chloride  and  this  method 
was  abandoned.  Instead,  the  hydrochloride  was  dissolved  in  water  and 
sodium  hydroxide  added  until  an  outside  test  with  phenolphthalein  showed 
a very  faint  alkaline  reaction.  The  solution,  after  filtering,  was  evaporated 
to  dryness  and  the  residue  was  ground  up  in  a mortar  with  alcohol,  the 
alcohol  filtered,  diluted  and  partially  evaporated.  The  slightly  turbid 
solution  was  filtered  through  charcoal  and  then  the  solution  was  evaporated 
until  only  a few  cubic  centimeters  of  liquid  were  left,  a large  mass  of  crys- 
tals having  separated  during  the  evaporation.  The  crystals  were  filtered 
off  and  recrystallized  by  evaporation  of  the  water  solution,  the  acid  being 
practically  as  soluble  in  cold  as  in  hot  water.  This  was  repeated  three 
times  more  and  the  acid  then  showed  no  trace  of  chlorine.  The  molecular 
weight  was  determined  with  this  sample.  Heated  in  a capillary  tube 
no  melting  point  was  obtained  but  considerable  decomposition  took  place 
between  300 0 and  320  °,  depending  upon  the  rate  of  heating. 

[a]^f°  = 67.0°;  0.207  g.  in  10  cc.  of  solution. 


Subst.,  0.418,  0.585;  H20,  15.6,  18.4;  depression,  0.25 1 °,  0.297  °;  mol.  wt.  found, 

.CH2— nh2 


196,  197.  Calc,  for  CsHk 


: 185. 


C02H 


CO 


a-Camphidone,  C8Hi4\  /NH. — This  was  prepared  from  the 

XCH/ 

hydrochloride  of  a-aminocampholic  acid  in  precisely  the  same  manner 
as  the  anhydride  of  aminocamphonanic  acid  was  prepared  from  the  hydro- 
chloride of  aminocamphonanic  acid.  After  making  the  acetic  anhydride 
solution  alkaline  with  sodium  hydroxide  the  same  liquid  layer  was  observed 
on  the  surface  that  was  observed  in  the  preparation  of  the  above  mentioned 
anhydride.  This  was  very  likely  the  acetyl  derivative,  but  no  attempt 
was  made  to  isolate  it.  Practically  a theoretical  yield  of  the  anhydride 
was  given.  It  melts  at  229-231  °.  Recrystallizing  once  from  petroleum 
ether  gave  a pure  product  melting  at  230-23 1°. 

[a]2D6°  = — 33-9°;  o-5  g.  in  10  cc.  alcohol  solution.  Rupe  and  Splittgerber1  give 
[q:]d  = — 37. 20  in  a 10%  solution  in  benzene. 

1 Ber.,  40,  4313  (1907).  • 


Calc,  for  C8HI4< 


C0- 

CH2 


\ 

/ 


NH:  N = 8.38;  found:  N = 8.42. 


Nitroso  Derivative  of 


a-Camphidone, 


8-tli4\^ 


CO 


CsH 


sNNO. — The 


NCH/ 

a-camphidone  was  dissolved  in  hydrochloric  acid  (1:4)  and  a sodium 
nitrite  solution  slowly  added.  The  yellow  crystals  formed  were  filtered, 
dried  and  recrystallized  from  hot  alcohol.  The  lemon  yellow,  needle-like 
crystals  gave  a melting  point  of  1 25-1 26°.  The  product  given  by  a second 
recrystallization  showed  the  same  melting  point. 


[«]2d  ° = — 59-0°;  0.25  g.  in  10  cc.  of  alcohol. 


From  analogy  to  the  well-known  nitroso  derivatives  of  aminocamphonanic 
and  dihydroaminocampholytic  acid  anhydrides,  it  was  not  thought 
necessary  to  analyze  the  compound  for  identification. 

/NH2 

Aminodihydrocampholytic  Acid,  C8Hi4\  . — This  acid  was  pre- 

XC02H 

pared  in  the  same  manner  as  described  by  Noyes1  except  that  a more 
elaborate  method  was  followed  in  recovering  the  last  traces  of  the  acid. 
The  procedure  followed  was  identical  with  that  for  the  preparation  of 
aminocamphonanic  acid  from  a-camphoramidic  acid,  except  that  0- 
camphoramidic  acid  was  used  and,  instead  of  adding  sufficient  hydro- 
chloric acid  to  give  the  acid  hydrochloride,  only  enough  was  added  to  give 
a solution  exactly  neutral  to  phenolphthalein.  After  this  point  the  solu- 
tion was  evaporated  until  the  sodium  chloride  was  starting  to  come  down. 
The  crystals  of  the  amino  acid  were  then  filtered  off  and  to  the  filtrate 
an  excess  of  hydrochloric  acid  was  added  and  the  whole  evaporated  to 
dryness,  and  the  residue  extracted  with  alcohol.  Since  the  dihydro- 
aminocampholytic acid  is  quite  easily  esterified,  the  alcoholic  solution  was 
diluted  with  considerable  water  and  just  enough  sodium  hydroxide  solution 
added  to  give  a solution  neutral  to  phenolphthalein.  It  was  then  partially 
evaporated  and  the  amino  acid  filtered  off.  An  excess  of  hydrochloric 
acid  was  added  to  this  filtrate  and  the  same  procedure  followed  as  above. 
Since  the  acid  is  no  more  soluble  in  hot  than  in  cold  water  and  is  not  soluble 
in  any  other  solvent  it  must  be  purified  by  dissolving  in  water  and  partial 
evaporation.  For  ordinary  purposes  one  recrystallization  is  sufficient. 
For  taking  the  molecular  weight  and  rotations  an  acid  was  used  which 
had  been  recrystallized  six  times,  two  more  times  than  was  necessary  to 
free  it  from  traces  of  chlorine. 

[a]2D°  = 54.7  °;  0.5  g.  in  10  cc.  of  water  solution.  Noyes  and  Phillips2  give  [«]d  = 

1 Am.  Chem.  J.,  16,  503  (1894). 

2 Ibid.,  24,  290  (1900). 


5 


53-7°  for  the  saturated  solution  (about  7.5%).  Subst.,  0.415,  0.613;  H20,  20.5,  21.2; 

/NH2 

depression,  0.199,  0.278;  mol.  wt.  found,  187, 191 ; Calc,  for  C8Hi4<f  : 171. 


'C02H 


Aminodihydrocampholytic  Acid  Hydrochloride,  C8Hi4 


/ 


NH3CI 


.—A 


'C02H 


few  grams  of  the  free  acid  were  shaken  with  a few  cc.  of  water  and  sufficient 
hydrochloric  acid  was  added  to  give  a green  color  to  methyl  violet  paper. 
The  solution  was  then  partially  evaporated  and  upon  allowing  to  cool 
the  hydrochloride  separated.  It  was  filtered  and  recrystallized  from  hot 
water.  A melting  point  of  262-263°  was  found.  Recrystallizing  again 
gave  a product  melting  at  261-262°,  which  is  the  same  as  that  reported 
by  Noyes.1 

41.3  °;  1 g.  in  10  cc.  of  water  solution. 


M2d6 


/ 


NH 


Aminodihydrocampholytic  Acid  Anhydride,  C8Hi4\*  I . — This  sub- 

xCO 

stance  was  prepared  either  by  treating  the  free  acid  with  acetic  anhydride 
or  by  treating  the  hydrochloride  of  the  acid  with  sodium  acetate  and 
acetic  anhydride  and  subsequently  heating  the  mixture  with  an  excess 
of  sodium  hydroxide.  In  the  latter  method  it  is  probable  that  the  acetyl 
derivative  is  formed,  as  the  similar  liquid  layer  was  always  formed  on 
addition  of  the  excess  of  sodium  hydroxide  to  the  acetic  anhydride  solu- 
tion. The  latter  method  of  preparation  has  the  advantage  of  allowing 
quite  impure  hydrochloride  to  be  used.  The  melting  point,  188-189°, 
and  the  specific  rotation,  [q:]d  = 72.8°,  have  already  been  published.2 

Nitroso  Derivative  of  Aminodihydrocampholic  Acid  Anhydride, 


C8Hi 


/ 


N NO 


'CO 


-Since  the  rotation  of  this  substance  had  never  been 


It  was  prepared  according 


reported  it  was  thought  desirable  to  obtain  it. 
to  a method  previously  reported.2 

[«]^>°  = — 83.3°;  0.25  g.  in  10  cc.  of  absolute  alcohol  solution. 

Cyanodihydrocampholytic  Acid. — Hoogewerf  and  Van  Dorp3  pre- 
pared this  acid  in  just  the  same  manner  that  they  prepared  the  cyano- 
camphonanic  acid.  Rupe  and  Splittgerber4  proceeded  in  essentially 
the  same  manner.  Starting  with  12.5  g.  of  /3-camphoramidic  acid  and 
proceeding  in  precisely  the  same  manner  as  in  the  preparation  of  the  cyano- 
camphonanic  acid,  9.5  g.  of  crude  acid  were  obtained,  which  is  an  80% 
yield.  There  was  not  nearly  as  much  tendency  to  form  a gummy  pre- 

1 Am.  Chem.  /.,  16,  504  (1894). 

2 Noyes  and  Potter,  J.  Am.  Chem.  Soc.,  34,  1072  (1912). 

3 Rec.  trav.  chim.,  14,  267  (1895). 

4 Ber.,  40,  4313  (1900). 


i6 


cipitate  as  was  noted  in  the  case  of  the  cyanocamphonanic  acid.  The 
crude  acid  was  purified  by  dissolving  in  8%  ammonia  and  precipitating 
with  hydrochloric  acid.  One  such  procedure  sufficed  to  bring  the  melt- 
ing point  up  to  109-110°.  A portion  was  recrystallized  again  in  the  same 
manner  but  no  change  in  the  melting  point  was  observed.  The  above 
is  the  melting  point  observed  by  Hoogewerf  and  Van  Dorp.1 

[a]2o°  = 25.3 °;  0.6  g.  in  10  cc.  of  alcohol  solution.  Hoogewerf  and  Van  Dorp 
give  the  specific  rotation  [c*]d  = 18.12  0 for  a 6%  alcohol  solution. 


Since  they  purified  their  acid  by  recrystallization  from  hot  water,  in  order 
to  clear  up  the  remote  possibility  of  this  causing  the  difference  in  the  ro- 
tation, some  of  the  crude  acid  was  purified  by  their  method,  but  a rotation 
taken  after  the  fourth  recrystallization,  gave  a value  [a]D  = 25.2 0 and 
after  the  fifth  recrystallization  [a]D  = 25.3 °,  so  there  is  little  doubt  but 
that  this  is  the  correct  value. 

/CH2NH3CI 

/3-Aminocampholic  Acid  Hydrochloride,  C8Hi4\  . — Starting 

xC02H 


with  cyanodihydrocampholytic  acid  the  procedure  for  the  preparation, 
separation,  and  purification  of  this  substance  was  the  same  as  the  prepa- 
ration of  the  a-aminocampholic  acid  hydrochloride.  It  was  found,  how- 
ever, that  the  reduction  in  the  case  in  hand  was  not  as  complete  as  with  the 
cyanocamphonanic  acid.  It  was  found  more  advisable  to  simply  separate 
the  unchanged  cyanoacid  by  extraction  of  the  acid  solution  with  ether 
than  to  use  more  sodium  and  alcohol.  The  /3-aminocampholic  acid  hydro- 
chloride is  somewhat  less  soluble  than  its  isomer  and  hence  it  is  more  easily 
purified.  After  two  recrystallizations  its  melting  point  was  218-220°. 
[o:]2d0  = 41 .3 0.5  g.  in  10  cc.  of  water  solution. 

yCH2NH2 

j3-Aminocampholic  Acid,  C8Hi4\  . — About  5 g.  of  the  pure 

xC02H 


hydrochloride  were  dissolved  in  the  minimum  amount  of  water  and  suffi- 
cient strong  sodium  hydroxide  solution  (3  cc.  = 1 g.)  was  added  to  give 
a solution  neutral  to  phenolphthalein.  The  free  acid,  which  was  pre- 
cipitated, was  filtered,  dissolved  in  hot  water,  partially  evaporated  and 
filtered.  This  was  repeated  until  a substance  free  from  chlorine  was  ob- 
tained, three  recrystallizations  in  all  being  required. 

[a]^°  = 16. 40;  0.25  g.  in  10  cc.  of  solution. 

Subst.,  0.318,  0.389;  H20,  22.1,  21.8;  depression,  0.133,  0.167;  mol.  wt.  found,  199, 
/CH2NH2 

197.  Calc,  for  CgHi4<^  : 185. 

xco2h 


0-Camphidone,  C8H 


NH. — This  compound  was  prepared  from 


1 Rec.  trav.  chim.,  14,  267  (1895). 


i7 


the  /3-aminocampholic  acid  hydrochloride  in  just  the  same  manner 
as  the  a-camphidone  was  prepared  from  the  cx-aminocampholic  acid. 


24° 


A melting  point  of  234-235 ° was  found  and  a specific  rotation  [a]n 
63.2°;  0.25  g.  in  5 cc.  of  alcohol  solution.  Rupe  and  Splittgerber1  report 
a melting  point  of  225  0 and  its  specific  rotation  [<x]D  = 66.5°  for  a 10% 
solution  in  benzene.  An  analysis  of  the  compound  was  made. 


Calc,  for  CsHi4 


/co\ 


NH  = 8.38;  found:  N = 8.37. 


/C°\ 

Nitroso  Derivative  of  /3-Camphidone,  C8Hi4\  /N  NO. — The  /3- 

XCH/ 

camphidone  was  dissolved  in  dilute  hydrochloric  acid  (1:4)  and  a sodium 
nitrite  solution  was  added.  The  yellow  precipitate  was  filtered  and  re- 
crystallized from  alcohol  two  times,  when  a melting  point  of  164-165 0 
is  given.  A portion  recrystallized  a third  time  showed  the  same  melting 
point. 

[a]2D°  = 103 °;  0.25  g.  in  10  cc.  of  solution. 


Summary. 

It  is  shown  in  this  paper  that  the  specific  rotations  of  some  amino  de- 
rivatives of  camphoric  acid  are  consistent  with  the  view  that  those  amino 
acids  which  can  form  cyclic  salts  containing  quinquivalent  nitrogen  and 


/C°\ 

a ring  of  six  atoms  form  salts  having  the  general  formula  R\  /O 

XNH3X 

in  aqueous  solutions.  Amino  acids  which  would  give  a ring  of  seven  atoms 
in  forming  a cyclic  salt  appear  to  exist  in  solution  as  compounds  of  the 


/C02H 

form,  R\  . These  relations  furnish  strong  evidence  that  nitrogen 
XNH2 


is  in  reality  quinquivalent  in  ammonium  salts  and  that  the  hydrogen 
of  the  acid  combines  with  the  nitrogen  instead  of  remaining  combined 
with  the  acid  radical,  as  Werner  has  supposed. 

Several  new  compounds  have  been  prepared  and  the  specific  rotations 
of  a number  of  known  compounds  have  been  determined. 

Urbana,  Illinois. 


ACKNOWLEDGMENT. 

This  investigation  was  carried  on  during  the  academic  year  1912- 1913 
and  was  undertaken  at  the  suggestion  of  Professor  W.  A.  Noyes.  This 
opportunity  is  gladly  taken  by  the  writer  to  express  his  sincere  apprecia- 
tion for  the  suggestions  which  Professor  Noyes  was  always  ready  to  give, 
and  still  more  for  the  inspiration  obtained  by  the  personal  association 
with  him  in  the  laboratory. 


BIOGRAPHICAL. 

The  writer  graduated  from  Lake  Forest  College  in  1909  with  the  degree  of 
Bachelor  of  Arts.  During  the  next  academic  year,  1909-1910,  he  was  As- 
sistant in  Chemistry  at  the  University  of  Illinois.  For  the  years  19 10-19 13 
he  was  Research  Assistant  to  Professor  W.  A.  Noyes.  While  holding 
the  latter  position,  investigations  on  molecular  rearrangements  in  the 
camphor  series  were  pursued.  The  results  obtained,  other  than  those 
described  in  the  present  paper,  were  published  in  the  Journal  of  the 
American  Chemical  Society  under  the  titles,  “Camphonolic  Acid  and 
Camphonololactone,”  Vol.  XXXIV,  pp.  62-67,  and  “Campholytic  Acid 
and  Related  Compounds,  Walden  Inversion,”  Vol.  XXXIV,  pp.  1067- 
1080.  In  19 1 1 he  received  the  degree  of  Master  of  Science  from  the 
University  of  Illinois. 

The  writer  is  a member  of  the  Gamma  Alpha  Scientific  Fraternity,  of 
Sigma  Xi,  of  the  Alpha  Chi  Sigma  and  Phi  Lambda  Upsilon  Chemical 
Fraternities,  and  of  the  American  Chemical  Society. 


